The mechanism of action and biological effects of epidermal growth factor (EGF) on liver will be studied using primary cultures of hepatocytes isolated from adult rats. Since EGF and insulin have been shown to have a synergistic action on liver, the role of these hormones in liver regeneration will be investigated. Studies using whole animals will be performed to investigate the processes involved in the regulation of blood levels of these hormones and how this might be linked to the regenerative processes in liver. A homogeneous population of adult rat liver parenchymal cells maintained as non-dividing primary cultures will be used as a model system to investigate the mechanism of action and biological effects of EGF on the liver. We have already determined that 125I-labeled EGF is capable of binding these cultured hepatocytes in a specific and saturable manner. Attempts will be made to determine if the membrane-bound 125I-EGF acts only on the external surface of the membrane, or whether it is capable of entering the hepatocyte as is the case for human fibroblasts. If it is suspected that 125I-EGF enters the cell, attempts will be made to determine the structural integrity of the molecule and whether it becomes associated with the nucleus or other sub-cellular organelles.